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Although NSAIDs have been associated with both reduced and increased cutaneous melanoma risk, few studies have examined these associations by ultraviolet radiation (UVR) or personal sun-sensitivity. We examined the associations between NSAID use and first primary invasive cutaneous melanoma among 58,227 non-Hispanic white participants in the United States Radiologic Technologists cohort study. Poisson regression was used to calculate rate ratios (RR) and 95% likelihood-based confidence intervals (CI), adjusting for attained age, birth cohort, and ambient UVR. No significant association of melanoma was observed for any use of NSAIDs (RR, 0.87; 95% CI, 0.71–1.09). The relative risks of melanoma for the highest categories of aspirin and other NSAID use (≥5 times per month vs. none) were 0.93 (95% CI, 0.74–1.16) and 1.02 (95% CI, 0.83–1.25), respectively. Further analyses did not reveal dose–response for trends in frequency of NSAID use or interactions with sex, UVR, eye and hair color, and skin complexion. In this large nationwide study, NSAID use was not associated with melanoma risk.Prevention Relevance:NSAIDs have been associated with both reduced and increased melanoma risk. However, few studies have examined the role of UVR or personal sun-sensitivity on these associations. Our findings strengthen the evidence that NSAID use is not associated with melanoma risk, even in sun-sensitive subgroups.

Although NSAIDs have been associated with both reduced and increased cutaneous melanoma risk, few studies have examined these associations by ultraviolet radiation (UVR) or personal sun-sensitivity. We examined the associations between NSAID use and first primary invasive cutaneous melanoma among 58,227 non-Hispanic white participants in the United States Radiologic Technologists cohort study. Poisson regression was used to calculate rate ratios (RR) and 95% likelihood-based confidence intervals (CI), adjusting for attained age, birth cohort, and ambient UVR. No significant association of melanoma was observed for any use of NSAIDs (RR, 0.87; 95% CI, 0.71–1.09). The relative risks of melanoma for the highest categories of aspirin and other NSAID use (≥5 times per month vs. none) were 0.93 (95% CI, 0.74–1.16) and 1.02 (95% CI, 0.83–1.25), respectively. Further analyses did not reveal dose–response for trends in frequency of NSAID use or interactions with sex, UVR, eye and hair color, and skin complexion. In this large nationwide study, NSAID use was not associated with melanoma risk. Prevention Relevance: NSAIDs have been associated with both reduced and increased melanoma risk. However, few studies have examined the role of UVR or personal sun-sensitivity on these associations. Our findings strengthen the evidence that NSAID use is not associated with melanoma risk, even in sun-sensitive subgroups.

Background Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk. Methods Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer. Results Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n Conclusion These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations, we identified a novel NRAS variant (c.170A>C, p.D57A) in a melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11 273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2+ binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A>C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted.

Background: Skin cancer screening is routinely performed for members of melanoma-prone families, but longitudinal studies evaluating the efficacy of surveillance in this high-risk population are lacking. Methods: We evaluated thickness for first primary melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) enrolled in NCT00040352 (NCI familial melanoma study) from 1976 through 2014; enrolled patients received routine skin cancer screening and education about skin self-exams. We used linear and ordinal logistic regression models adjusted for gender and age with a generalized estimating equations approach to report changes in thickness and tumor (T) stage over time, comparing outcomes for NCI cases diagnosed before (pre-study) versus after study participation (prospective) and for NCI cases versus nonfamilial cases [Surveillance, Epidemiology, and End Results (SEER) 9 registries]. Results: Tumor thickness was evaluated for 293 NCI (pre-study = 246; prospective = 47) patients. Compared with NCI pre-study cases, NCI prospective melanomas were thinner (0.6 vs. 1.1 mm; P < 0.001) and more likely to be T1 stage [39/47 (83%) vs. 98/246 (40%); P < 0.001]. Similar findings (P < 0.05) were observed for familial cases with and without germline CDKN2A and CDK4 mutations. Peters–Belson modeling suggested that calendar period effects of decreasing thickness in the general population (SEER 9) did not fully explain thickness trends in NCI families. Conclusions: Participation in a longitudinal surveillance program providing skin cancer screening and education about skin self-exams was associated with thinner melanomas for members of melanoma-prone families. Impact: The study findings support the clinical benefit of screening (physician and self) for this high-risk population.

Antiretroviral therapy (ART) may alter susceptibility to nonkeratinocyte skin cancers (NKSCs) by improving immunity in people living with HIV (PLWH). Using linked data from HIV and cancer registries in 12 US states/regions during the ART era (1996-2018), we calculated standardized incidence ratios (SIRs) for 27 NKSCs comparing incidence to the general population. Risk factors for NKSCs were evaluated using Poisson regression. There were 2,743 NKSCs diagnosed in 585,706 PLWH followed for 4,575,794 person-years. Kaposi sarcoma (KS) was the most common cancer (82%) followed by melanoma (12%) and cutaneous lymphoma (2.6%). Incidence was elevated for virus-related NKSCs: KS (SIR 147, 95%CI 141-153), diffuse large B-cell lymphoma (DLBCL, 5.19, 3.13-8.11), and Merkel cell carcinoma (MCC, 3.15, 1.93-4.87); elevated incidence for DLBCL and MCC was observed only among PLWH with a prior AIDS diagnosis. KS risk was highest among men who have sex with men. Incidence was not increased for melanoma, adnexal carcinomas, and sarcomas. Melanoma and MCC arose disproportionately on sun-exposed skin, supporting a role for ultraviolet radiation in their development. In conclusion, risk for most NKSCs was similar to the general population during the ART era, suggesting that PLWH without NKSC risk factors may not require intensive skin surveillance.

STUDY QUESTION Are reproductive factors and exogenous hormone use associated with incidence of cutaneous melanoma while accounting for ultraviolet radiation (UVR) exposure across different life periods and sun sensitivity factors? SUMMARY ANSWER Earlier age at menarche and late age at first birth, but not other estrogen-related factors were associated with an increased incidence rate of melanoma, with higher risks observed for earlier age at menarche and light hair color at age 15 years. WHAT IS KNOWN ALREADY Although estrogens have been recognized as photosensitizing, previous studies have reported inconsistent findings for the association of melanoma with estrogen-related factors. Most have not collected detailed skin cancer risk factors and have not thoroughly investigated effect modification by ambient UVR and sun sensitivity. STUDY DESIGN, SIZE, DURATION Participants in the US Radiologic Technologists study, an occupational cohort of 146 022 radiologic technologists (73% women), were included and followed during the four time periods (1983–1989, 1994–1998, 2003–2005 and 2012–2014). PARTICIPANTS/MATERIALS, SETTING, METHODS Non-Hispanic white female participants who completed both the second (baseline) and third questionnaires, and did not report having cancer (except keratinocyte carcinoma) at baseline, were included and followed from their age at completion of the second (baseline) questionnaire until the earlier of first primary cancer diagnosis, including invasive melanoma of the skin, or completion of either the third or fourth questionnaire. Reproductive and exogenous hormonal factors were ascertained from the second (baseline) questionnaire, which also collected information on demographic, lifestyle factors and sun sensitivity factors. Ambient UVR was assigned by linking geocoded residential locations, based on self-reported residential history information collected from the third questionnaire to satellite-based ambient UVR data from the National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer database. To examine the association of reproductive factors, exogenous hormone use, and first primary invasive melanoma of the skin, we used Poisson regression to calculate rate ratios (RRs) and 95% likelihood-based CIs, adjusting for attained age, birth cohort, lifetime average annual ambient UVR, contraceptives and menopausal hormone therapy use. To address the effect modification of ambient UVR exposure and sun sensitivities on melanoma risk, we conducted likelihood-ratio tests for multiplicative interaction. MAIN RESULTS AND THE ROLE OF CHANCE Over a median follow-up time of 17.1 years, 0.95% of eligible participants had an incident first primary melanoma (n = 444). Higher melanoma incidence rates were observed in participants with older attained age, blue/green/gray eye color, blonde/red/auburn natural hair color at age 15, fair skin complexion, and higher UVR. We found an increased incidence rate of melanoma in women who experienced menarche at an earlier age (13, 12 and LIMITATIONS, REASONS FOR CAUTION Information on reproductive history and exogenous hormone use was self-reported. We did not have information on specific doses or formulations of exogenous hormone medications or breastfeeding. WIDER IMPLICATIONS OF THE FINDINGS Women residing in areas of high ambient UVR and those with blonde/red/auburn natural hair color may constitute an additional high-risk group in need of more frequent skin cancer screening. Identifying susceptible periods of exposure or factors that modify UVR susceptibility may aid in guiding more targeted guidelines for melanoma prevention. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

BACKGROUND: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. OBJECTIVE: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. METHODS: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and non-carriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family. RESULTS: Histologic slides were evaluated for 290 melanomas (139 from 132 non-carriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in the majority of invasive melanomas from POT1 carriers (10 of 15 [67%], P

The characterization of the effects of solar UVR on a broad set of circulating markers in systemic immunity and inflammation may provide insight into the mechanisms responsible for the UVR associations observed for several benign and malignant diseases. We examined the associations between exposure to solar UVR and circulating levels of 78 markers among 1,819 individuals aged 55–74 years who participated in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial using multiplex assays. Solar UVR was derived by linking the geocoded locations of 10 screening centers across the continental United States and the date of blood draw to the National Solar Radiation Database from 1993 to 2005. We assessed associations between ambient solar UVR and dichotomized marker levels using adjusted weighted logistic regression models and applied a 5% false discovery rate criterion to P-values. UVR exposure was associated (P < 0.05) with 9 of the 78 markers. CCL27, CCL4, FGF2, GM-CSF, IFN-γ, soluble IL4R, IL-7, and IL-11 levels were lower with increasing UVR tertile, with adjusted ORs ranging from 0.66 to 0.80, and the significant association for CCL27 withstood multiple comparison correction. In contrast, CRP levels were elevated with increasing UVR. Solar UVR was associated with alterations in systemic immune and inflammation marker levels., Graphical abstract

BACKGROUND: Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest. METHODS: We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 individuals in the ASPirin in Reducing Events in the Elderly Trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed preenrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (low-risk [0%-20%], medium-risk [21%-80%], high-risk [81%-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma. RESULTS: At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20 to 1.77) and prevalent melanoma (odds ratio [OR] = 1.55 per SD, 95% CI = 1.42 to 1.69). Participants in the highest-risk PRS group had increased risk compared with the low-risk group for incident melanoma (OR = 2.51, 95% CI = 1.28 to 4.92) and prevalent melanoma (OR = 3.66, 95% CI = 2.69 to 5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma. CONCLUSIONS: A genomic risk score is associated with melanoma risk in older individuals and may contribute to targeted surveillance.

IMPORTANCE: Nonkeratinocyte skin cancers are an important cause of morbidity and mortality for immunosuppressed solid organ transplant recipients (SOTRs), but the spectrum of disease and risk factor characteristics are unknown. OBJECTIVE: To characterize the spectrum of disease and risk factors for common and rare nonkeratinocyte skin cancers in SOTRs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included 444 497 SOTRs who underwent a transplant in the US between January 1, 1987, and December 31, 2017, using linked data from the national transplant registry and 32 cancer registries. Data analysis was conducted from April 1, 2021, to September 30, 2021. MAIN OUTCOMES AND MEASURES: Standardized incidence ratios (SIRs) were used to assess risk relative to the general population, and Poisson regression was used to evaluate risk factors. RESULTS: A total of 2380 nonkeratinocyte skin cancers were identified among 444 497 SOTRs (median age at transplant, 50 years; range, 0-96 years; 274 276 [61.7%] male; 272 241 [61.2%] non-Hispanic White). Melanoma was the most common cancer (1471 [61.8%]), followed by Merkel cell carcinoma (334 [14.0%]), Kaposi sarcoma (186 [7.8%]), sebaceous carcinoma (170 [7.1%]), and cutaneous lymphomas (108 [4.5%]). Risks were most strongly elevated for cancers associated with viruses, including Kaposi sarcoma (SIR, 20.5; 95% CI, 17.7-23.7), Merkel cell carcinoma (SIR, 16.2; 95% CI, 14.5-18.1), and extranodal natural killer/T-cell lymphoma (SIR, 44.3; 95% CI, 5.37-160). Risks were also significantly elevated for sebaceous carcinoma (SIR, 15.2; 95% CI, 13.0-17.7), anaplastic large cell lymphoma (SIR, 6.82; 95% CI, 4.53-9.85), and diffuse large B-cell lymphoma (SIR, 5.17; 95% CI, 3.28-7.76). Several characteristics were independently associated with greater risk for multiple skin cancer types, including male sex, older age at transplant, factors associated with UV radiation exposure (non-Hispanic White race and ethnicity, living in an area with higher UV radiation exposure, and posttransplant diagnosis of keratinocyte carcinoma), and increasing time since transplantation. Treatment with mammalian target of rapamycin inhibitors was associated with reduced melanoma incidence (incidence rate ratio, 0.75; 95% CI, 0.57-0.98). A total of 847 skin cancers (39.4%) occurred on the head and neck. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that viruses, UV radiation exposure, and immunosuppression are associated with the development of skin cancer in SOTRs. Certain high-risk subgroups may benefit from increased skin surveillance, and treatment with mammalian target of rapamycin inhibitors could be effective for melanoma chemoprevention in the transplant population.

Importance Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P

BACKGROUND: Skin cancer screening is routinely performed for members of melanoma-prone families, but longitudinal studies evaluating the efficacy of surveillance in this high-risk population are lacking. METHODS: We evaluated thickness for first primary melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) enrolled in NCT00040352 (National Cancer Institute [NCI] familial melanoma study) from 1976 through 2014; enrolled patients received routine skin cancer screening and education about skin self-exams. We used linear and ordinal logistic regression models adjusted for gender and age with a generalized estimating equations approach to report changes in thickness and tumor (T) stage over time, comparing outcomes for NCI cases diagnosed before (“pre-study”) vs. after study participation (“prospective”) and for NCI cases vs. non-familial cases (Surveillance, Epidemiology, and End Results [SEER] 9 registries). RESULTS: Tumor thickness was evaluated for 293 NCI (pre-study=246; prospective=47) patients. Compared to NCI pre-study cases, NCI prospective melanomas were thinner (0.6mm vs. 1.1mm; P

Sebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Finally, we review the clinical implications of recent advances in sebaceous carcinoma research for screening, prevention, and treatment.

Sebaceous carcinoma (SC) is an aggressive skin tumor. Although ultraviolet radiation (UVR) is an important risk factor for some skin cancer types, no population-level study has evaluated for an association between UVR and SC risk. Herein, we examined satellite-based ambient UVR in relation to SC incidence using Surveillance, Epidemiology, and End Results 18 cancer registry data (2000–2016). There were 3503 microscopically confirmed cases of SC diagnosed during the study period. For non-Hispanic whites, there was an association between increasing ambient UVR and SC risk (incidence rate ratio [per UVR quartile] = 1.15, 95% confidence interval = 1.11 to 1.19; two-sided P

CDKN2A and CDK4 are well-established melanoma susceptibility genes, but their effect on tumor location and distribution is unknown. We used a case-case study design to assess for differences in tumor location between mutation carriers (CDKN2A = 141 patients, 348 melanomas; CDK4 = 15 patients, 54 melanomas) and noncarriers (104 patients, 157 melanomas) in US melanoma-prone families. Associations between groups were assessed with chi-square tests. Odds ratios (ORs) for tumor location were adjusted for diagnosis age, gender, and superficial spreading subtype. Models included random effects to account for within individual and family correlations. Compared with having a truncal melanoma, CDK4 (vs. noncarriers: lower extremities OR = 14.5, 95% confidence interval [CI] = 5.02-42.0, P0.001; upper extremities OR = 6.88, 95% CI = 2.37-19.9, P0.001; head and neck OR = 18.6, 95% CI = 4.04-85.2, P0.001) and CDKN2A (vs. noncarriers: lower extremities OR = 3.01, 95% CI = 1.56-5.82, P0.05; upper extremities OR = 1.91, 95% CI = 1.03-3.52, P 0.05; head and neck OR = 5.40, 95% CI = 2.10-13.9, P0.001) carriers had higher odds of developing melanoma at all other sites. Similar findings were observed for analyses stratified by gender, age, and first versus subsequent melanoma diagnoses. Further studies are needed to understand the biology underlying these genotype-associated patterns of tumor development, which could provide new insights into melanoma treatment and prevention.

Background Teledermatology may improve dermatologic care access in underserved areas and expand the clinical experience of dermatologists-in-training. The potential for teledermatology to supplement global health curricula in dermatology residency education has not been explored. Methods An international virtual grand rounds (VGR) curriculum was created based on teledermatology cases from Kabul, Afghanistan. The learning objectives included understanding the diagnosis and management of skin diseases in unfamiliar resource-limited settings and highlighting socioeconomic, cross-cultural, and ethical issues. A 17-item, Likert scale questionnaire was used to assess the effectiveness of the curriculum, including specific Accreditation Council for Graduate Medical Education (ACGME) competencies, as well as interest in global health and teledermatology. Results The survey was completed by 85 of 118 VGR attendees (72% response rate). Most respondents considered the curriculum valuable to their education (mean 4.5 on a 5-point Likert scale; standard deviation, 0.5), learned more about diagnosis and treatment of skin diseases in international settings (4.5; 0.6) and in the US (4.1; 0.8), and learned more about socioeconomic, cultural, and ethical issues in skin health (4.6; 0.5). The majority also reported being more interested in global dermatology (4.1; 0.8) and would recommend VGR to a colleague (4.5; 0.6). Conclusion This pilot curriculum provided an innovative platform to enhance undergraduate and graduate medical education in international dermatology. International teledermatology education may be used to address multiple ACGME core competencies and increase resident awareness of sociocultural determinants of skin health.

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density.

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density.

Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine whether long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of US children (N=5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios (ORs) were calculated for the patient-evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR=0.90, 95% confidence interval (CI): 0.87–0.93, P

Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell-cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%-100%) and intensity (0-3) of reactivity. A score of 0-300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9-279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9-199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

The purpose of this study was to identify the presence or absence of geographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers (DFU) and lower extremity amputations (LEA).Diabetic beneficiaries with foot ulcers (n=682,887) and lower extremity amputations (n=151,752) were enrolled in Medicare Parts A and B during the calendar year 2007. We used ordinary least squares (OLS) regression to explain geographic variation in per capita Medicare spending and one-year mortality rates.Health care spending and mortality rates varied considerably across the nation for our two patient cohorts. However, higher spending was not associated with a statistically significant reduction in one-year patient mortality (P=.12 for DFU, P=.20 for LEA). Macrovascular complications for amputees were more common in parts of the country with higher mortality rates (P.001), but this association was not observed for our foot ulcer cohort (P=.12). In contrast, macrovascular complications were associated with increased per capita spending for beneficiaries with foot ulcers (P=.01). Rates of hospital admission were also associated with higher per capita spending and increased mortality rates for individuals with foot ulcers (P.001 for health spending and mortality) and lower extremity amputations (P.001 for health spending, P=.01 for mortality).Geographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers and amputations is associated with regional differences in the utilization of inpatient services and the prevalence of macrovascular complications.

Author(s): Shi, Lucy L; Sargen, Michael R; Chen, Suephy C; Arbiser, Jack L; Pollack, Brian P | Abstract: Background: Botulinum toxin type A (BTX-A) injections are an effective treatment for controlling hyperhidrosis at sites of amputation. Hyperesthesia associated with amputated limbs is a major barrier to performing this procedure under local anesthesia.Objective: To present a novel method for improving local anesthesia with BTX-A injections.Methods a Results: A 29-year-old military veteran with a below-the-knee amputation of his right leg was suffering from amputation site hyperhidrosis, which was impeding his ability to comfortably wear a prosthesis. Prior to presenting to our clinic, the patient received one treatment of BTX-A injections to his amputation stump while under general anesthesia for surgical repair of trauma-related injuries. In our dermatology clinic, we repeated the procedure using topical lidocaine-prilocaine (30 gm total) for local anesthesia. This provided effective relief of hyperhidrosis for 6 months, but the procedure was very painful (9/10 intensity). We repeated the same procedure 6 months later, using ice in addition to topical lidocaine-prilocaine (30 gm) for local anesthesia; this resulted in reduced pain (3/10 intensity) for the patient.Conclusions: We suggest using ice in combination with a topical anesthetic as an effective method for pain control that avoids general anesthesia in treating amputation-associated hyperhidrosis.

Purpose: Male breast cancer has been linked extensively to mutations of BRCA2 and, to a lesser extent, BRCA1. The aim of this study was to perform a comprehensive analysis of point mutations and genomic rearrangements in the BRCA1 and BRCA2 genes in 41 men with breast cancer. Patients and Methods: Deleterious point mutations were identified in 15 men (37%): 4 (10%) and 11 (27%) in BRCA1 and BRCA2, respectively. In the remaining 26 men, we screened for large genomic rearrangements in BRCA1 and BRCA2 using multiplex ligation-dependent probe amplification. Results: We did not detect any large genomic rearrangements. Men with BRCA1 or BRCA2 mutations were more likely to have a family history of prostate cancer (P = 0.025). Three of 4 male breast tumors with BRCA1 mutations (75%) were estrogen receptor positive. Whereas some studies have reported an 8%-0 rate of large BRCA2 genomic rearrangement in familial male breast cancer cases, we did not detect any such genomic rearrangements in BRCA1 or BRCA2 for our cohort. Conclusion: Despite this negative finding, our study, to the best of our knowledge, is one of the first to comprehensively screen for mutations, including large genomic rearrangement mutations, in BRCA1 and BRCA2 in men with breast cancer in the United States.

Background Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective We sought to identify associations between histology of melanomas and CDKN2A genotype. Methods This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations. Results Compared with CDKN2A − cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation ( P trend = .02) and increased pagetoid scatter ( P trend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A − (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.

Prescription rates for diabetic drugs vary considerably across the United States for Medicare beneficiaries. The goal of this study was to determine if non-clinical factors (patient race, ethnicity, gender, income) are associated with regional variation in pharmacotherapy decisions for diabetic patients enrolled in Medicare.We performed a spatially-weighted, linear regression analysis of the entire diabetic population enrolled in Medicare Parts A, B, and D for the years 2006 through 2009. Our outcomes of interest were the percentage of diabetic patients being treated with metformin, a sulfonylurea, a thiazolidinedione, or insulin within a hospital referral region (HRR).Prescription rates for metformin, sulfonylureas, thiazolidinediones, and insulin varied more than two-fold between hospital referral region. Metformin prescription rates were increased in western states while prescription rates for sulfonylureas and insulins were highest in the South and Midwest. In contrast with these other diabetic drug classes, members of the thiazolidinedione drug class were prescribed more frequently in the Central United States (Great Plains, Colorado Rockies, Northern Texas, Oklahoma). Prescription rates for each drug class were increased in hospital referral regions with a lower household income. Referral regions with larger African American populations were associated with higher prescription rates for insulin (p0.001) and lower prescription rates for metformin (p0.001). Gender and Hispanic ethnicity were not associated with regional variation in prescription rates for the four major diabetic drug classes.Geographic differences exist in the management of type 2 diabetes for Medicare enrollees. Prescription patterns were associated with household income and African American race. Further studies are necessary to identify local, unidentified factors that might be influencing provider management styles.

Background Based on the goals of health care reform, growth in the demand for health care will continue to increase the demand for physicians and, as physician shortages widen, advanced practice nurses (APNs) and physician assistants (PAs) will play larger roles. Together with physicians they constitute a workforce of "advanced clinicians." The objective of this study was to assess the capacity of this combined workforce to meet the future demand for clinical services. Study Design Projections were constructed to the year 2025 for the supply of physicians, APNs, and PAs, and these were compared with projections of the demand for advanced clinical services, based on federal estimates of future spending and historic relationships between spending and the health care labor force. Results If training programs for APNs and PAs grow as currently projected but physician residency programs are not further expanded, the aggregate per capita supply of advanced clinicians will remain close to its current level, which will be 20% less than the demand in 2025. Increasing the numbers of entry-level (PGY1) residents by 500 annually will narrow the gap, but it will remain >15%. Conclusions The nation faces a substantial shortfall in its combined supply of physicians, APNs, and PAs, even under aggressive training scenarios, and deeper shortages if these scenarios are not achieved. Efforts must be made to expand the output of clinicians in all 3 disciplines, while also strengthening the infrastructure of clinical practice and facilitating the delegation of tasks to a broadened spectrum of caregivers in new models of care.

Background Recent studies have shown that breast cancer detected by screening has a more favorable prognosis than interval breast cancer. To further understand the biologic significance of this finding, we investigated the association of disease recurrence, local and distant, with the method of detection of the primary breast cancer in a cohort of 1686 women treated with breast conservation. Patients and Methods The charts of 1686 women with primarily stage I or II invasive breast cancer treated by breast conservation between 1977 and 2002 were reviewed. The median length of follow-up was 6 years. Univariate and multivariate analyses using binary logistic regression were performed for 2 subgroups: (1) those with local recurrence versus those without; and (2) those with distant metastasis versus those without distant metastasis. Results Our data confirmed several of the well-known risk factors for local and distant recurrence. In addition, we found that individuals with breast cancer detected on physical examination alone have a significantly higher risk for local recurrence compared with patients with cancer detected on mammogram alone, independent of tumor size (odds ratio [OR], 2.369; 95% CI, 1.235-4.547; P = .01). We also found a similar correlation for risk of distant metastasis in these 2 groups of women (OR, 2.201; 95% CI, 1.211-3.998; P = .01). Conclusion Breast cancers that are palpable might represent an aggressive biologic subtype with an increased risk of local and distant recurrence. Risk stratification might need to include this clinical feature in addition to conventional prognostic factors.

10512 Introduction: Prophylactic mastectomy (PM) reduces breast cancer risk by >90% in women who are carriers of deleterious BRCA1 or BRCA2 mutations. Genetic testing prior to breast cancer surgery has been reported to affect PM decision in high-risk patients. The ideal timing of genetic testing as well as the clinical characteristics of affected mutation carriers electing PM remain unclear. This is a pilot study to identify significant clinical characteristics associated with affected carriers who had undergone PM. Methods: Retrospective chart review was performed on 103 breast cancer affected BRCA1 or BRCA2 mutation carriers that were seen at our high risk clinic who had undergone genetic testing between 1995 and 2005. Clinical characteristic, initial surgery treatment modalities, and dates of genetic testing and prophylactic mastectomy were collected and analyzed using the chi-square or Fisher exact tests. Results: Of the 103 affected mutation carriers, 30 (29%) underwent prophylactic mastectomy (PM) where as 73 (71%) did not (no PM). Ethnicity, age of diagnosis, tumor size, nodal status, family history and initial breast cancer surgery types (BCT vs. mastectomy) were not significantly different between the two groups. Of the 30 women who underwent PM, 19 (63%) vs. 9 (30%) underwent PM before and after their genetic testing respectively. Of the 19 women who had PM before their genetic testing, 4 (21%) had BCT as initial treatment whereas 15 (78.9%) had mastectomy as initial treatment and 9 of 15 (60%) had synchronous contralateral prophylactic mastectomy. For the 9 women who had PM after their genetic testing, 5 (56%) had BCT vs. 4 (44%) had mastectomy as their initial surgical treatment (p < 0.001). Conclusion: In this study, we found a significant correlation between the initial breast cancer surgical modality of mastectomy with women undergoing prophylactic mastectomy. The impact of family history of breast cancer does not appear to be significant. Physician recommendations or patient preference are unknown. Our data suggest that high risk women who elect mastectomy as their initial surgical management to treat their breast cancer are more likely to undergo prophylactic mastectomy regardless of knowledge of their mutation status. No significant financial relationships to disclose.